Practice parameters for the use of actigraphy in the military operational context: the Walter Reed Army Institute of Research Operational Research Kit-Actigraphy(WORK-A)

Background: The Walter Reed Army Institute of Research(WRAIR) Operational Research Kit-Actigraphy(WORK-A) is a set of unique practice parameters and actigraphy-derived measures for the analysis of operational military sleep patterns. The WORK-A draws on best practices from the literature and comprises 15 additional descriptive variables. Here, we demonstrate the WORK-A with a sample of United States Army Reserve Officers’ Training Corps(ROTC) cadets(n=286) during a month-long capstone pre-commissioning training exercise.Methods: The sleep of ROTC cadets(n=286) was measured by Philips Actiwatch devices during the 31-day training exercise. The preliminary effectiveness of the WORK-A was tested by comparing differences in sleep measures collected by Actiwatches as calculated by Philips Actiware software against WORK-A-determined sleep measures and self-report sleep collected from a subset of ROTC cadets(n=140).Results: Actiware sleep summary statistics were significantly different from WORK-A measures and self-report sleep(P≤0.001). Bedtimes and waketimes as determined by WORK-A major sleep intervals showed the best agreement with self-report bedtime(22:21±1:30 vs. 22:13±0:40, P=0.21) and waketime(04:30±2:17 vs. 04:31±0:47, P=0.68). Though still significantly different, the discrepancy was smaller between the WORK-A measure of time in bed(TIB) for major sleep intervals(352±29) min and self-report nightly sleep duration [(337±57) min, P=0.006] than that between the WORK-A major TIB and Actiware TIB [(177±42) min, P≤0.001].Conclusions: Default actigraphy methods are not the most accurate methods for characterizing soldier sleep, but reliable methods for characterizing operational sleep patterns is a necessary first step in developing strategies to improve soldier readiness. The WORK-A addresses this knowledge gap by providing practice parameters and a robust variety of measures with which to profile sleep behavior in service members.

Sleep disturbances and predictors of nondeployability among active-duty army soldiers: an odds ratio analysis of medical healthcare data from fiscal year 2018

Background:The impact of sleep disorders on active-duty soldiers’medical readiness is not currently quantified.Patient data generated at military treatment facilities can be accessed to create research reports and thus can be used to estimate the prevalence of sleep disturbances and the role of sleep on overall health in service members.The current study aimed to quantify sleep-related health issues and their impact on health and nondeployability through the analysis of U.S.military healthcare records from fiscal year 2018(FY2018).Methods:Medical diagnosis information and deployability profiles(e-Profiles)were queried for all active-duty U.S.Army patients with a concurrent sleep disorder diagnosis receiving medical care within FY2018.Nondeployability was predicted from medical reasons for having an e-Profile(categorized as sleep,behavioral health,musculoskeletal,cardiometabolic,injury,or accident)using binomial logistic regression.Sleep e-Profiles were investigated as a moderator between other e-Profile categories and nondeployability.Results:Out of 582,031 soldiers,48.4%(n=281,738)had a sleep-related diagnosis in their healthcare records,9.7%(n=56,247)of soldiers had e-Profiles,and 1.9%(n=10,885)had a sleep e-Profile.Soldiers with sleep e-Profiles were more likely to have had a motor vehicle accident(p OR(prevalence odds ratio)=4.7,95%CI 2.63–8.39,P≤0.001)or work/duty-related injury(p OR=1.6,95%CI 1.32–1.94,P≤0.001).The likelihood of nondeployability was greater in soldiers with a sleep e-Profile and a musculoskeletal e-Profile(p OR=4.25,95%CI 3.75–4.81,P≤0.001)or work/dutyrelated injury(p OR=2.62,95%CI 1.63–4.21,P≤0.001).Conclusion:Nearly half of soldiers had a sleep disorder or sleep-related medical diagnosis in 2018,but their sleep problems are largely not profiled as limitations to medical readiness.Musculoskeletal issues and physical injury predict nondeployability,and nondeployability is more likely to occur in soldiers who have sleep e-Profiles in addition to these issues.Addressing sleep problems may prevent accidents and injuries that could render a soldier nondeployable.

Longitudinal association of gonorrhea and bacterial vaginosis with repeat chlamydia diagnoses among U.S. Army women: A retrospective cohort analysis

Background: Historically, sexually transmitted infections have affected the health of the U.S. military. To determine whether gonorrhea, bacterial vaginosis, genital herpes, and trichomoniasis are predictors of repeat chlamydia diagnoses among U.S. Army women, medical data reported into the Defense Medical Surveillance System during the 2006–2012 period were analyzed.Methods: For all inpatient and outpatient medical records, the first and second International Classification of Diseases,version 9(ICD-9) diagnostic positions were reviewed for each chlamydia case to determine the occurrence of repeat diagnoses. The Andersen-Gill regression model, an extension of the Cox model for multiple failure-time data, was used to study associations between predictors and repeat chlamydia diagnoses.Results: Among 28,201 women with a first chlamydia diagnosis, 5145(18.2%), 1163(4.1%), 267(0.9%), and 88(0.3%)had one, two, three, and four or more repeat diagnoses, respectively. Overall, the incidence of repeat chlamydia was8.31 cases per 100 person-years, with a median follow-up time of 3.39 years. Gonorrhea(hazard ratio(HR)=1.58, 95%CI: 1.44–1.73) and bacterial vaginosis(HR=1.40, 95% CI: 1.09–1.79) were significant predictors for repeat chlamydia.These estimated hazard ratios were attenuated, but remained significant, after controlling for age, race/ethnicity,marital status, and military rank. No significant association was found for genital herpes(HR=1.13, 95% CI: 0.55–2.29)and trichomoniasis(HR=1.43, 95% CI: 0.43–4.68).Conclusions: This large cohort study suggests that gonorrhea and bacterial vaginosis were associated with repeat chlamydia diagnoses among U.S. Army women. These findings can be used in formulating new interventions to prevent repeat chlamydia diagnoses.

First molecular identification of multiple tick‑borne pathogens in livestock within Kassena‑Nankana,Ghana

The risk of pathogen transmission continues to increase significantly in the presence of tick vectors due to the trade of livestock across countries.In Ghana,there is a lack of data on the incidence of tick-borne pathogens that are of zoonotic and veterinary importance.This study,therefore,aimed to determine the prevalence of such pathogens in livestock using molecular approaches.A total of 276 dry blood spots were collected from cattle(100),sheep(95)and goats(81)in the Kassena-Nankana Districts.The samples were analyzed using Polymerase Chain Reaction(qPCR)and conventional assays and Sanger sequencing that targeted pathogens including Rickettsia,Coxiella,Babesia,Theileria,Ehrlichia and Anaplasma.An overall prevalence of 36.96%was recorded from the livestock DBS,with mixed infections seen in 7.97%samples.Furthermore,the prevalence of infections in livestock was recorded to be 19.21%in sheep,14.13%in cattle,and 3.62%in goats.The pathogens identified were Rickettsia spp.(3.26%),Babesia sp.Lintan(8.70%),Theileria orientalis(2.17%),Theileria parva(0.36%),Anaplasma capra(18.48%),Anaplasma phagocytophilum(1.81%),Anaplasma marginale(3.26%)and Anaplasma ovis(7.25%).This study reports the first molecular identification of the above-mentioned pathogens in livestock in Ghana and highlights the use of dry blood spots in resource-limited settings.In addition,this research provides an update on tick-borne pathogens in Ghana,suggesting risks to livestock production and human health.Further studies will be essential to establish the distribution and epidemiology of these pathogens in Ghana.

Refinement of saliva microRNA biomarkers for sports-related concussion

Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging evidence that salivary micro-ribonucleic acids(miRNAs)may serve as biomarkers of concussion;however,it remains unclear whether concussion-related miRNAs are impacted by exercise.We sought to determine whether40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports.Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.Methods:This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites.Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing.Within-subjects testing was used to identify and exclude miRNAs that changed with either(a)a single episode of exercise(166 samples from 83 individuals)or(b)season-long participation in contact sports(212 samples from 106 individuals).The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression(172 samples from 75 concussed and 97 non-concussed individuals).Results:Two miRNAs(miR-532-5p and miR-182-5p)decreased(adjusted p<0.05)after a single episode of exercise,and 1 miRNA(miR-4510)increased only after contact sports participation.Twenty-three miRNAs changed at the end of a contact sports season.Two of these miRNAs(miR-26b-3p and miR-29c-3p)were associated(R>0.50;adjusted p<0.05)with the number of head impacts sustained in a single football practice.Among the 15 miRNAs not confounded by exercise or season-long contact sports participation,11 demonstrated a significant difference(adjusted p<0.05)between concussed and non-concussed participants,and 6 displayed moderate ability(area under curve>0.70)to identify concussion.A single ratio(miR-27a-5p/miR-30a-3p)displayed the highest accuracy(AUC=0.810,sensitivity=82.4%,specificity=73.3%)for differentiating concussed and non-concussed participants.Accuracy did not differ between participants with SRC and non-SRC(z=0.5,p=0.60).Conclusion:Salivary miRNA levels may accurately identify SRC when not confounded by exercise.Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive,sideline adjunct for SRC assessment.

Bacterial vaginosis:a synthesis of the literature on etiology,prevalence,risk factors,and relationship with chlamydia and gonorrhea infections

Bacterial vaginosis(BV) is a common vaginal disorder in women of reproductive age. Since the initial work of Leopoldo in 1953 and Gardner and Dukes in 1955, researchers have not been able to identify the causative etiologic agent of BV. There is increasing evidence, however, that BV occurs when Lactobacillus spp., the predominant species in healthy vaginal flora, are replaced by anaerobic bacteria, such as Gardenella vaginalis, Mobiluncus curtisii, M. mulieris, other anaerobic bacteria and/or Mycoplasma hominis. Worldwide, it estimated that 20%–30% of women of reproductive age attending sexually transmitted infection(STI) clinics suffer from BV, and that its prevalence can be as high as 50%–60% in high-risk populations(e.g., those who practice commercial sex work(CSW). Epidemiological data show that women are more likely to report BV if they: 1) have had a higher number of lifetime sexual partners; 2) are unmarried; 3) have engaged in their first intercourse at a younger age; 4) have engaged in CSW, and 5) practice regular douching. In the past decade, several studies have provided evidence on the contribution of sexual activity to BV. However, it is difficult to state that BV is a STI without being able to identify the etiologic agent. BV has also emerged as a public health problem due to its association with other STIs, including: human immunodeficiency virus(HIV), herpes simplex virus type 2(HSV-2), Chlamydia trachomatis(CT) and Neisseria gonorrhoeae(NG). The most recent evidence on the association between BV and CT/NG infection comes from two secondary analyses of cohort data conducted among women attending STI clinics. Based on these studies, women with BV had a 1.8 and 1.9-fold increased risk for NG and CT infection, respectively. Taken together, BV is likely a risk factor or at least an important contributor to subsequent NG or CT infection in high-risk women. Additional research is required to determine whether this association is also present in other low-risk sexually active populations, such as among women in the US military. It is essential to conduct large scale cross-sectional or population-based case-control studies to investigate the role of BV as a risk factor for CT/NG infections. These studies could lead to the development of interventions aimed at reducing the burden associated with bacterial STIs worldwide.

Subchronic Oral Toxicity of Pyridostigmine Bromide in Rats

This study evaluated the oral toxicity of pyridostigmine bromide in Sprague-Dawley rats when administered for 13 weeks by daily gavage. Groups of 10 rats/sex received doses of 0, 5, 15, 30, or 60 mg/kg/day. Toxicity was limited to exaggerated cholinergic stimulation at doses of 15 mg/kg/day or greater. Significant findings included tremors and inhibition of RBC acetylcholinesterase. Thus, 5 mg/kg/day of pyridostigmine bromide appears to be the no observed toxic effect level under the conditions of the present investigation.

Synthesis of Substituted Benzothiazepine Compounds with Medicinal Potential

A versatile synthetic approach toward a series of benzothiazepines with medicinal potential (for example, compound 1) that allows incorporation of structural variation at the three aromatic regions of the structure, and at the sulfur atom, was developed. Knoevenagel condensation of indan-1,3-diones with benzaldehydes, yielded 2-benzylidineindan-1,3-diones, which undewent thio-Michael addition and intramolecular imine formation upon reaction with 2-aminothiophenols, to produce the target benzothiazepines. Use of indan-1,3-diones, benzaldehydes or 2-aminothiophenols bearing further substitution enabled production of novel 5,11-dihydro-12H-benzo[b]indeno [1,2-e][1,4]thiazepin-12-one analogs 1 - 14, including compounds bearing substitution at novel positions within the scaffold.

Regioselective Synthesis and Biological Evaluation of 1-Hydroxyl Modified Ailanthinone Derivatives as Antimalarials

The triterpene quassinoid ailanthinone is a structurally intricate natural product possessing highly potent antimalarial activity against multidrug resistance plasmodium parasites. Although the mechanism of action of ailanthinone is not completely understood, it is presumed to disrupt regular ribosomal functions by inhibiting parasite protein synthesis. Natural scarcity and low solubility of many quassinoids have impeded their development as potential clinical candidates, but exquisite potency of ailanthinone against Plasmodium remains compelling in the global fight against malaria. Herein, we report the highly selective synthesis of 1-hydroxyl derivatives of ailanthinone, including ester, carbonate, carbamate and sulfonate derivatives. The key feature of the synthesis is a one-step regioselective modification of the 1-hydroxyl group in favor of two other hydroxyl groups at C12 and C13. Derivatives were obtained via direct reaction with acyl/sulfonyl chlorides in the presence of a tertiary amine base without any protection-deprotection. In vitro antimalarial evaluations of these derivatives were compared with chloroquine and mefloquine against the Plasmodium falciparum clones, D6, W2, and TM91C235. The results demonstrate that modification of the 1-hydroxyl group is achievable, and the antimalarial activity of these derivatives relative to the parent product is significantly retained, thus paving the way for synthesis of derivatives with improved biological availability and/or increased potency.

Crimean-Congo hemorrhagic fever virus in Central,Eastern,and South-eastern Asia

Crimean-Congo hemorrhagic fever(CCHF),caused by Crimean-Congo hemorrhagic fever virus(CCHFV),is endemic in Africa,Asia,and Europe,but CCHF epidemiology and epizootiology is only rudimentarily defined for most regions.Here we summarize what is known about CCHF in Central,Eastern,and South-eastern Asia.Searching multiple international and country-specific databases using a One Health approach,we defined disease risk and burden through identification of CCHF cases,anti-CCHFV antibody prevalence,and CCHFV isolation from vector ticks.We identified 2313 CCHF cases that occurred in 1944–2021 in the three examined regions.Central Asian countries reported the majority of cases(2,026).In Eastern Asia,China was the only country that reported CCHF cases(287).In South-eastern Asia,no cases were reported.Next,we leveraged our previously established classification scheme to assign countries to five CCHF evidence levels.Six countries(China,Kazakhstan,Kyrgyzstan,Tajikistan,Turkmenistan,and Uzbekistan)were assigned to level 1 or level 2 based on CCHF case reports and the maturity of the countries’surveillance systems.Two countries(Mongolia and Myanmar)were assigned to level 3 due to evidence of CCHFV circulation in the absence of reported CCHF cases.Thirteen countries in Eastern and South-eastern Asia were categorized in levels 4 and 5 based on prevalence of CCHFV vector ticks.Collectively,this paper describes the past and present status of CCHF reporting to inform international and local public-health agencies to strengthen or establish CCHFV surveillance systems and address shortcomings.